Cost-effective 3D scanning and printing technologies for outer ear reconstruction: Current status

Current 3D scanning and printing technologies offer not only state-of-the-art developments in the field of medical imaging and bio-engineering, but also cost and time effective solutions for surgical reconstruction procedures. Besides tissue engineering, where living cells are used, bio-compatible polymers or synthetic resin can be applied. The combination of 3D handheld scanning devices or volumetric imaging, (open-source) image processing packages, and 3D printers form a complete workflow chain that is capable of effective rapid prototyping of outer ear replicas. This paper reviews current possibilities and latest use cases for 3D-scanning, data processing and printing of outer ear replicas with a focus on low-cost solutions for rehabilitation engineering

Managing trap-nesting bees as crop pollinators : Spatiotemporal effects of floral resources and antagonists

The decline of managed honeybees and the rapid expansion of mass-flowering crops increase the risk of pollination limitation in crops and raise questions about novel management approaches for wild pollinators in agroecosystems. Adding artificial nesting sites, such as trap nests, can promote cavity-nesting bees in agroecosystems, but effectiveness could be limited by the availability of floral resources in the surrounding landscape and by natural antagonists. In two European regions, we exposed artificial trap nests in paired field boundaries adjacent to oilseed rape (OSR) fields or non-flowering crops for 2 years within 32 landscapes covering two independent gradients of OSR cover and semi-natural habitat (SNH) cover in the landscape. We analysed the effects of local and landscape-wide floral resource availability, land-use intensity, landscape complexity and natural antagonists on community composition and population dynamics of trap-nesting bees. Numbers of brood cells showed a strong, three-fold increase in response to the additional nesting sites. Species richness and abundance of cavity-nesting bees that were active during OSR flowering increased significantly with increasing amounts of early season landscape-wide floral resource availability, such as the cultivation of OSR. Later foraging species benefited instead from the availability of late-season alternative flower resources or SNH cover once the mass-flowering had ceased. Density-dependent parasitism increased following mass-flowering, while no density-dependent effect was found during mass-flowering. Structural equation modelling revealed that the influence of floral resource availability on community growth rate was mediated by community size. Community size showed a strong negative effect on community growth rate. Despite positive density-dependent parasitism, antagonists had only weak regulating effects on community growth rate. Synthesis and applications. Trap-nesting bee populations grow markedly with the increasing availability of food resources in the landscape and effectiveness of trap nests is only marginally limited by natural antagonists. Thus, trap nests could be a simple pollinator-supporting strategy to accompany the current expansion of mass-flowering crops and to ensure pollination services for insect-pollinated crops. Trap nests benefit, not only early season active generalist bees during oilseed rape flowering, but also species with later phenology if accompanied by other pollinator-supporting practices.</p

Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation

Background: The success of a cochlear implant (CI), which is the standard therapy for patients suffering from severe to profound sensorineural hearing loss, depends on the number and excitability of spiral ganglion neurons (SGNs). Brain-derived neurotrophic factor (BDNF) has a protective effect on SGNs but should be applied chronically to guarantee their lifelong survival. Long-term administration of BDNF could be achieved using genetically modified mesenchymal stem cells (MSCs), but these cells should be protected – by ultra-high viscous (UHV-) alginate (‘alginate-MSCs’) – from the recipient immune system and from uncontrolled migration.Methods: Brain-derived neurotrophic factor-producing MSCs were encapsulated in UHV-alginate. Four experimental groups were investigated using guinea pigs as an animal model. Three of them were systemically deafened and (unilaterally) received one of the following: (I) a CI; (II) an alginate-MSC-coated CI; (III) an injection of alginate-embedded MSCs into the scala tympani followed by CI insertion and alginate polymerization. Group IV was normal hearing, with CI insertion in both ears and a unilateral injection of alginate-MSCs. Using acoustically evoked auditory brainstem response measurements, hearing thresholds were determined before implantation and before sacrificing the animals. Electrode impedance was measured weekly. Four weeks after implantation, the animals were sacrificed and the SGN density and degree of fibrosis were evaluated.Results: The MSCs survived being implanted for 4 weeks in vivo. Neither the alginate-MSC injection nor the coating affected electrode impedance or fibrosis. CI insertion with and without previous alginate injection in normal-hearing animals resulted in increased hearing thresholds within the high-frequency range. Low-frequency hearing loss was additionally observed in the alginate-injected and implanted cochleae, but not in those treated only with a CI. In deafened animals, the alginate-MSC coating of the CI significantly prevented SGN from degeneration, but the injection of alginate-MSCs did not.Conclusion: Brain-derived neurotrophic factor-producing MSCs encapsulated in UHV-alginate prevent SGNs from degeneration in the form of coating on the CI surface, but not in the form of an injection. No increase in fibrosis or impedance was detected. Further research and development aimed at verifying long-term mechanical and biological properties of coated electrodes in vitro and in vivo, in combination with chronic electrical stimulation, is needed before the current concept can be tested in clinical trials

Lipidic nanocapsule drug delivery: neuronal protection for cochlear implant optimization

Objective: Sensorineural hearing loss leads to the progressive degeneration of spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which should be suppressed to assure a close nerve–electrode interaction, the density of healthy SGC is one factor that influences the efficiency of cochlear implants (CI), the choice of treatment for affected patients. Rolipram, a phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory effects and might also reduce SGC degeneration and fibrosis, but it has to pass the cellular membrane to be biologically active. Methods: Lipidic nanocapsules (LNC) can be used as biodegradable drug carriers to increase the efficacy of conventional application methods. We examined the biological effects of rolipram and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor necrosis factor-α (TNF-α) production in vitro and on SGC survival in systemically-deafened guinea pigs in vivo. Results: Our results prove that rolipram does not have a beneficial effect on cultured SGC. Incorporation of rolipram in LNC increased the survival of SGC significantly. In the DC study, rolipram significantly inhibited TNF-α in a dose-dependent manner. The rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo data do not confirm the in vitro results. Conclusion: By transporting rolipram into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in vitro, but not in vivo. This might be due to dilution of test substances by perilymph or an inadequate release of rolipram based on differing in vivo and in vitro conditions. Nevertheless, based on in vitro results, proving a significantly increased neuronal survival when using LNC-rolipram compared to pure rolipram and pure LNC application, we believe that the combination of rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after CI implantation. We conclude that rolipram is a promising drug that can be used in inner ear therapy and that LNC have potential as an inner ear drug-delivery system. Further experiments with modified conditions might reveal in vivo biological effects

ACEMg-mediated hearing preservation in cochlear implant patients receiving different electrode lengths (PROHEARING): study protocol for a randomized controlled trial

Abstract Background The indications for a cochlear implant (CI) have been extended to include patients with some residual hearing. Shorter and thinner atraumatic electrodes have been designed to preserve the residual hearing in the implanted ear. However, the insertion of the electrode array into the cochlea, with potential mechanical trauma and the presence of this foreign body inside the cochlea, may lead to free radical formation and reduced blood perfusion of the cochlea which can result in the loss of residual hearing. Methods/design In this single-center, randomized, placebo-controlled, double-blind phase II clinical trial the effect of free radical scavengers and a vasodilator on the residual hearing of 140 CI patients will be evaluated. The formulation is composed of β-carotene (vitamin A), ascorbic acid (vitamin C), dl-α-tocopherol acetate (vitamin E) and the vasodilator magnesium (Mg), or ACEMg. Medication is administered twice daily per os for approximately 3 months. The primary measure is based upon the reduction in postoperative low-frequency air-conducted pure-tone thresholds compared to preoperative thresholds in ACEMg-treated patients compared to those of a placebo group. Additionally, the effect of different electrode lengths (20, 24 and 28 mm) is analyzed. Study visits are scheduled 2 days before surgery, at first fitting, which is the adjustment and start of stimulation via CI 4 weeks after surgery and 3, 6, 9 and 12 months after first fitting. The primary endpoint is the air-conduction hearing loss at 500 Hz 3 months after first fitting. Additionally, speech recognition tests, hearing aid benefit in the implanted ear and electrophysiological measurements of implant function are assessed. Since this is a blinded clinical trial and recruitment is still ongoing, data continue to accrue and we cannot yet analyze the outcome of the ACEMg treatment. Discussion There is an unfulfilled need for new strategies to preserve acoustic hearing in CI patients. This study will provide first-in-man data on ACEMg-mediated protection of residual hearing in CI patients. Performing all surgeries and patient follow-up at one study site improves consistency in diagnosis and therapy and less variability in surgery, audiological test techniques and fitting. This approach will allow investigation of the influence of ACEMg on residual hearing in CI patients. Trial registration The German Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) application number 4039192, was registered on 6 December 2013 with protocol amendment version 3.0 from 19 August 2014. EudraCT number: 2012-005002-22 .http://deepblue.lib.umich.edu/bitstream/2027.42/134623/1/13063_2016_Article_1526.pd

Coating stability and insertion forces of an alginate-cell-based drug delivery implant system for the inner ear

Long-term drug delivery to the inner ear for neuroprotection might improve the outcome for hearing disabled patients treated with a cochlear implant (CI). Neurotrophic factor (NTF) producing cells encapsulated in an alginate-matrix, to shield them from the host immune system and to avoid migration, and applied as viscose solution or electrode coating could address this requirement. Both application methods were tested for their feasibility in an artificial human cochlea model. Since both strategies potentially influence the electrode implantability, insertion forces and coating stability were analyzed on custom-made electrode arrays. Both, injection of the alginate-cell solution into the model and a manual dip coating of electrode arrays with subsequent insertion into the model were possible. The insertion forces of coated arrays were reduced by 75% of an uncoated reference. In contrast, filling of the model with non-crosslinked alginate-cell solution slightly increased the insertion forces. A good stability of the coating was observed after first insertion (85%) but abrasion increased after multiple insertions (50%). Both application strategies are possible options for cell-induced drug-delivery to the inner ear, but an alginate-cell coating of CI-electrodes has a great potential to combine an endogenous NTF-source with a strong reduction of insertion forces

Mass-flowering crops dilute pollinator abundance in agricultural landscapes across Europe

Mass-flowering crops (MFCs) are increasingly cultivated and might influence pollinator communities in MFC fields and nearby semi-natural habitats (SNHs). Across six European regions and 2 years, we assessed how landscape-scale cover of MFCs affected pollinator densities in 408 MFC fields and adjacent SNHs. In MFC fields, densities of bumblebees, solitary bees, managed honeybees and hoverflies were negatively related to the cover of MFCs in the landscape. In SNHs, densities of bumblebees declined with increasing cover of MFCs but densities of honeybees increased. The densities of all pollinators were generally unrelated to the cover of SNHs in the landscape. Although MFC fields apparently attracted pollinators from SNHs, in landscapes with large areas of MFCs they became diluted. The resulting lower densities might negatively affect yields of pollinator-dependent crops and the reproductive success of wild plants. An expansion of MFCs needs to be accompanied by pollinator-supporting practices in agricultural landscapes

The neural bases of tinnitus : Lessons from deafness and cochlear implants

Subjective tinnitus is the conscious perception of sound in the absence of any acoustic source. The literature suggests various tinnitus mechanisms, most of which invoke changes in spontaneous firing rates of central auditory neurons resulting from modification of neural gain. Here, we present an alternative model based on evidence that tinnitus is: (i) rare in people who are congenitally deaf, (ii) common in people with acquired deafness, and (iii) potentially suppressed by active cochlear implants used for hearing restoration. We propose that tinnitus can only develop after fast auditory fiber activity has stimulated the synapse formation between fast-spiking parvalbumin positive (PV+) interneurons and projecting neurons in the ascending auditory path and co-activated fronto-striatal networks after hearing onset. Thereafter, fast auditory fiber activity promotes feedforward and feedback inhibition mediated by PV+ interneuron activity in auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, and augmentation of auditory responses in central auditory pathways (neural gain) after damage of slow auditory fibers. When fast auditory fiber activity is lost, tonic PV+ interneuron activity is diminished, resulting in the prolonged response latencies, sudden hyperexcitability, enhanced cortical synchrony, elevated spontaneous gamma oscillations, and impaired attention/stress-control that have been described in previous tinnitus models. Moreover, because fast processing is gained through sensory experience, tinnitus would not exist in congenital deafness. Electrical cochlear stimulation may have the potential to re-establish tonic inhibitory networks and thus suppress tinnitus. The proposed framework unites many ideas of tinnitus pathophysiology and may catalyze cooperative efforts to develop tinnitus therapies

The interplay of landscape composition and configuration: new pathways to manage functional biodiversity and agroecosystem services across Europe

Managing agricultural landscapes to support biodiversity and ecosystem services is a key aim of a sustainable agriculture. However, how the spatial arrangement of crop fields and other habitats in landscapes impacts arthropods and their functions is poorly known. Synthesising data from 49 studies (1515 landscapes) across Europe, we examined effects of landscape composition (% habitats) and configuration (edge density) on arthropods in fields and their margins, pest control, pollination and yields. Configuration effects interacted with the proportions of crop and non‐crop habitats, and species’ dietary, dispersal and overwintering traits led to contrasting responses to landscape variables. Overall, however, in landscapes with high edge density, 70% of pollinator and 44% of natural enemy species reached highest abundances and pollination and pest control improved 1.7‐ and 1.4‐fold respectively. Arable‐dominated landscapes with high edge densities achieved high yields. This suggests that enhancing edge density in European agroecosystems can promote functional biodiversity and yield‐enhancing ecosystem services